It is known that 5(6)-substituted benzimidazole-2-carbamate derivatives of the formula (I) ##STR3## can be used in therapy due to their anthelmintic effect.
In the following formulae the definition of the substituents is as follows:
A stands for S, SO or SO.sub.2, PA1 R.sup.1 stands for a C.sub.1-4 alkyl group, PA1 R.sup.2 stands for C.sub.1-4 alkyl, C.sub.3-7 cycloalkyl or C.sub.6-10 aryl or aralkyl, PA1 n stands for 1, 2 or 3.
In order to indicate the position of the 5(6) substituent we may hereinafter refer to a 5-substituent, but we do not wish thereby to fix the position.
The compounds and their synthesis are described in the following patents: GB Nos. 1,123,317, 1,464,326, 1,455,728, DE No. 2,438,120, BE No. 817,364 and U.S. Pat. Nos. 3,738,993 and 4,076,827.
For the preparation of 5(6)-alkyl-sulfenyl-derivatives of the formula (IV) ##STR4## a process is further disclosed in Hungarian patents Nos. 182,763 and 182,782 and in Hungarian patent application No. 4725/84.
The common feature of the processes directed to the preparation of the above compounds is that the sulfinyl group is obtained by using various oxidizing agents such as hydrogen peroxide, peracetic acid, m-chloro-perbenzoic acid from a suitable sulfenyl and the difference is only whether the already prepared alkyl-sulfenyl-benzimidazole is oxidized or the starting 1,2-N-substituted alkyl-sulfenyl-benzene is oxidized which is suitable for the preparation of the latter compound.
According to the above mentioned patents the formation of the 5-alkyl-sulfenyl-group can be performed essentially by the following three methods:
1. 1,2-N-substituted-4-halogen-benzene or 5-halogen-benzimidazole-2-carbamate is reacted with alkali-mercaptide or sodium-hydrogene-sulfide followed by reaction with alkyl or aryl-halide.
2. Thio-cyanic-acid-ester is obtained from 1,2-N-substituted-4-halogen-benzene or 5(6)-halogen-benzimidazole-2-carbamate with alkali-rhodanide and the thio-cyanic-acid-ester is further reacted with alkyl or aryl-halide to produce a thio-ether (HU No. 182,763).
3. The 1,2-N-substituted benzene or benzimidazole-2-carbamate is sulfo-chlorinated at the 5(6)-position and the obtained sulfo-chloride is reduced to mercaptan or disulfide and the thio-ether is prepared from the obtained mercaptan or disulfide by reaction with alkyl or aryl halide (HU No. 182,782 or Hungarian patent application No. 4725/84).
The common feature of the mentioned reaction methods is the formation of the molecule in several steps and the yield of the individual steps is much lower than required to be economical and due to the various possibilities of side-reactions no homogeneous product is obtained.
The sulphinyl derivatives of the formula (V) ##STR5## can be prepared by the known oxidation of the 5-alkyl-sulphenyl derivative (HU No. 169,272).